Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: Are mesenchymal stromal cells involved in scar formation?

In this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues, specific collagen cross-linking routes are followed. In skin the cross-linking of the pyridinium type is normally very low; however, in different forms of fibrosis increased levels of this type of cross-linking have been found. The enzyme lysyl hydroxylase-2b (LH-2b) plays a crucial role in this type of cross-linking. The gene expression levels of LH-2b, alpha-smooth muscle actin, and collagen types I and III were determined in dermis, subcutaneous fat, and (hypertrophic) scar tissue as well as in isolated cultured mesenchymal cells derived from these tissues, by real-time RT-polymerase chain reaction. Cultured mesenchymal cells from fat and scar tissue as well as the tissues itself showed significantly higher expression of LH-2b, alpha-SMA, and collagen type I than dermal mesenchymal cells. LH-2b-dependent pyridinium cross-linking was significantly enhanced in fat and scar tissue compared with dermis. FACS analysis was performed to characterize the fibroblast-like cells from the dermis, fat, and scar tissue. All cell populations express the distinct pattern of CD markers also expressed by mesenchymal stromal cells. Furthermore, parts of these cell populations were able to differentiate into adipocytes, chondrocytes, and osteoblasts. We conclude, therefore, that mesenchymal (stem) cells from the subcutaneous fat might be responsible for the accumulation of collagen in these scars.